Effect of ipratropium bromide on airway and pulmonary muscarinic receptorsin a rat model of chronic obstructive pulmonary disease

Objective To observe the level of muscarinic receptors in airway and lung t issues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). Methods This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Musc arinic receptors in airway and lung tissues of normal rats, ipratropium bro mide-treated COPD rats and the recovering COPD rats were measured by the ra dio-ligand binding assay. Results Airway/lung pathology and pulmonary function tests showed that chro nic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues o f COPD rats were not changed compared with those of normal control rats (0. 030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the musc arinic receptors were not changed after inhalation of ipratropium bromide f or 5 days, but increased significantly after inhalation for 30 days, as com pared with those of the untreated COPD rats. The muscarinic receptors retur ned the normal levels at day 6 after cessation of ipratropium bromide treat ment. There were no differences among different groups of rats in equilibri um dissociation constants (Kd). Conclusion A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no s ignificant change in the number and function of muscarinic receptors in air way and lung tissues of the COPD rats, but upregulation of the muscarinic r eceptors was observed after long-term inhalation of ipratropium bromide.